This study was conducted to evaluate the cardiovascular risk of prescribing up to 90 mg of methylphenidate (MPD) daily for treating cocaine dependence. This within-subject study was completed in an inpatient setting. It was non-blinded for MPD dose and single-blinded for cocaine dose. Each patient was given intravenous cocaine at 0, 20 and 40 mg while at three different steady state levels of MPD (0, 60 and 90 mg). Seven non-treatment seeking cocaine addicts, who were recruited from the community, completed the study. There were no cardiac rhythm abnormalities noted except for sinus tachycardia and sinus bradycardia. There were no incidences of seizures or myocardial ischemia. In a repeated measures ANOVA, MPD was shown to have an independent positive effect on heart rate (p=0.0001) but not on SBP or DBP. There was no cocaine by MPD interaction for any vital sign. Peak systolic blood pressure (SBP) and diastolic blood pressure (DBP) for any patient up to 60 minutes after infusion was 169 mm and 108 mm, respectively. The first occurred when 60 mg of MPD and placebo cocaine were given and the second when no MPD and placebo cocaine were given. Peak heart rate for any patient up to 60 min after infusion was 143/min at 60 mg of MPD and 40mg of cocaine. The number of adverse events reported when cocaine and MPD were given together was less than the number reported when either drug was given alone. The adverse events reported when cocaine and MPD were given together included headache, nervousness, and lightheadedness. Subjective ratings of drug effect revealed that MPD did not enhance patients' response to, or desire for, cocaine. MPD appears to be a safe drug to use in cocaine addicts who continue to use cocaine at the dosages tested.